nonalcoholic fatty liver disease

Nonalcoholic Fatty Liver Disease

Stephanie H. Abrams, MD, MSAssistant Professor of Pediatrics

Baylor College of MedicineMedical Director-Kamp K’aana

[email protected]

NASH: a typical case 57 year old white female with elevated LFTs in

2008 No symptoms; history of obesity, type 2

diabetes, hypertension, hyperlipidemia, depression/anxiety

Meds: metformin, olmesartan/HCTZ, thyroxine, alprazolam, metoprolol, sertraline, clonidine, vitamins

SH: Occasional alcohol; nonsmoker PE: BMI 41 kg/m2

Lab: ALT 77, AST 81, AP 179, T bili 0.3, gluc 199, plts 168, INR 1.1

NASH: a typical case

Liver biopsy: NASH, NAS 4, stage 2 with extensive periportal fibrosis Plan: weight loss, exercise Follow up at 6 months: "No

symptoms"; "working on wt loss" PE: weight down 3 lbs/6 months

NASH: a typical case Admitted after no follow up x 2 years

Increased abdominal girth, dyspnea, leg edema

Wt up 60 lbs in 6 weeks Minor MVA with confusion Interim diagnosis: obstructive sleep apnea PE: Ascites, 3+ leg edema, alert/oriented Lab: ALT 55, AST 102, Alb 2.6, INR 1.7,

MELD 15, plts 149 CT: nodular liver, splenomegaly,

perisplenic varices, moderate ascites

NASH: a typical case Abdominal CT:

NASH: a typical case

Summary: Progression of NASH to cirrhosis

in setting of obesity, DM2, HTN Near normal liver enzymes

Prevalence of NAFLD in Adults NAFLD was present in 46% of all subjects by ultrasound (n=400)

74% of diabetics

Prevalence higher in men (58.9%)

Most common in Hispanics (58.3%), Caucasians (44.4%), African Americans (35.1%)

NAFLD patients: Were more likely to have HTN, higher BMI, & DM Ate more fast food & exercised less

NASH present in 12.2% of all adults Present in 22.2% of diabetics Advanced fibrosis in 22.5% 30% of all of those with NAFLD

Williams CD, et al. Gastroenterology 2011; 140: 124-131

NASH: 12%

Prevalence of NAFLD in Children Fatty liver was present in 13% of all subjects

Prevalence higher in boys (11.1%) compared with girls (7.9%)

Prevalence increases with age 17.3% for ages 15-19 years

NASH present in 3% of all children

Schwimmer, et al. Pediatrics 2006

Schwimmer, et al. Schwimmer, et al. Pediatrics Pediatrics 20062006

Prevalence of Fatty Liver by Race/Ethnicity

0

5

10

15

Black White Asian Hispanic

Pe

rce

nta

ge

•Using a logistic regression model, the Using a logistic regression model, the odds ratio for the presence of fatty odds ratio for the presence of fatty liver in Hispanics was 5.0liver in Hispanics was 5.0

NASH as an indication for transplant

*PN = Probable NASH based on risk factorsBrandman et al, AASLD 2011

*

Primary Diagnoses for Patients Transplanted in 2006

05

1015

20253035

Hepat

itis

C

Alcoho

lic C

irrhos

is

NASH

Crypt

ogenic

Cirr

hosis

PSC

Biliar

y Cirr

hosis

Other

Cirr

hosi

s

Met

abolic

Dis

ease BA

Retra

nspla

nt G

raft

Failu

re

Mal

ignan

cy

Other

Pe

rce

nt

NASH Accounted for 10.3% of all Liver Transplantation at the Cleveland Clinic in 2006

10.3%12.8%

33.1%

www.clevelandclinic.org

Pathogenesis: new ideas

“Two hit” vs lipotoxicity

Triglyceride

VLDL(secreted)

Hepatocellularfree fatty

acids

B Tetri

De novolipogenesis

Excesscarbohydrates

Excess peripheral lipolysis

Increasedcirculatingfatty acids

Insulin resistanc

e

Diet,uncontrolleddiabetes

Liver fat metabolism:Liver fat metabolism:

Lipiddroplets

(steatosis)

Triglyceride

VLDL(secreted)

Hepatocellularfree fatty

acids

NASH

B Tetri

Peroxisomalβ-oxidation

Mitochondrialβ-oxidation

SER (P450)ω-oxidation

ROS

ROS = reactive oxygen species

“Two-hit” hypothesis:“Two-hit” hypothesis:

De novolipogenesis

Excesscarbohydrates


Insulin resistanc

e



1

2

Lipotoxicmetabolites


Lipiddroplets

(steatosis)


Triglyceride


VLDL(secreted)

De novolipogenesis

Excesscarbohydrates

• ER stress• Inflammation• Apoptosis• Necrosis

Hepatocellularfree fatty acids


Insulin resistance


B Tetri

Lipotoxicity hypothesis:Lipotoxicity hypothesis:

Neuschwander-Tetri BA. Hepatology, 52:774-788, 2010


NASH



Lipiddroplets

(steatosis)


Triglyceride


VLDL(secreted)

De novolipogenesis

Excesscarbohydrates




Insulin resistance


B Tetri Neuschwander-Tetri BA. Hepatology, 52:774-788, 2010


NASH

• Ceramides• Diacylglycerols• Lysophosphatidyl choline• Others

Lipotoxicity hypothesis:Lipotoxicity hypothesis:



Lipiddroplets

(steatosis)


Triglyceride


VLDL(secreted)

De novolipogenesis

Excesscarbohydrates




Insulin resistance


B Tetri

Treatment of NASHTreatment of NASH

Neuschwander-Tetri BA. Hepatology, 52:774-788, 2010


NASH

• Weight loss• Exercise• TZDs?

Divert to muscle• Exercise

• Cut the carbs!

Facilitate storage/secretion

• Betaine?

Diminish toxicity

• Vitamin E?• Fish oil?• Ursodiol?

Divert to muscle• Exercise

NASH and the Metabolic Syndrome

NASH

Bad diet+

Obesity+

Sedentary+

Geneticpredisposition

Excesscirculating

NEFALipotoxic

intermediatesin the liver

Increasedliver triglyceride Steatosis

IR

NEFA: nonesterified fatty acids, ie, free fatty acidsIR: insulin resistancePCOS: polycystic ovary syndrome

β-oxidation

NASHRenin-

angiotensinactivation

DiabetesHyperinsulinemiaPCOS

HypertriglyceridemiaHypercholesterolemia

Cancer

Sleepapnea

Excesscirculating

NEFA

Lipotoxicintermediatesin the liver

Increasedliver triglyceride Steatosis

IR

NEFA: nonesterified fatty acids, ie, free fatty acidsIR: insulin resistancePCOS: polycystic ovary syndrome

β-cellloss

HTN

β-oxidation

Vascular disease

CAD/PVD

Bad diet+

Obesity+

Sedentary+

Geneticpredisposition

NASH and the Metabolic Syndrome

Treatment of NASH Lifestyle modification remains the

primary treatment recommendation Neuschwander-Tetri, B. A. Lifestyle modification as the primary

treatment of NASH. Clinics in Liver Disease (2009) 13: 649-665 Harrison, S. A. and Day, C. P. Benefits of lifestyle modification in

NAFLD. Gut (2007) 56: 1760-1769. Sullivan, S. Implications of diet on nonalcoholic fatty liver disease. Curr

Opin Gastroenterol (2010) 26: 160-164.

Bariatric surgery Pillai, A. A. and Rinella, M. E. Non-alcoholic fatty liver disease: is

bariatric surgery the answer? Clinics in Liver Disease (2009) 13: 689-710.

Drugs Ratziu, V. and Zelber-Sagi, S. Pharmacologic therapy of non-alcoholic

steatohepatitis. Clinics in Liver Disease (2009) 13: 667-688. Trial results

NASH CRN PIVENS trial

Pioglitazone vs Vitamin E vs Placebo in adults

Excluded diabetics, cirrhotics

PIVENS Study Design

placebo

Pioglitazone (30 mg/day)

Vitamin E (rrr α-tocopherol) 800 IU/day

RandomizationEligibility assessed by local pathologist

(1:1:1)Wk 0

Month -6

End of treatmentLiver Biopsy

Wk 96

Week 120end of study

Liver biopsy

N Engl J Med (2010) 362: 1675-1685

PIVENS Primary endpoint:

Decrease in NAS by 2 or more points, with at least a 1 point drop in ballooning, and no worsening of fibrosis

2 Primary comparisons: Vitamin E vs placebo Pioglitazone vs placebo

Significance set at p< 0.025

Secondary endpoints: changes in individual histologic features resolution of steatohepatitis changes in anthropometrics, insulin resistance, quality of life adverse events

N Engl J Med (2010) 362: 1675-1685

Vitamin E alone met the pre-specified primary endpoint

Vit E placebo Pio0

10

20

30

40

50

treatment groups

Pro

po

rtio

n o

f su

bje

cts

(%) P< 0.001 P< 0.04

36/84NNT=4.4

26/80NNT= 6.6

16/83

Both vitamin E and pioglitazone increased the proportion of subjects with resolution of NASH

Vitamin E placebo pioglitazone0

20

40

60

80

100

study groups

pro

po

rtio

n o

f su

bje

cts

(%)

P< 0.0008 P< 0.01

44/84

23/83

40/80

N Engl J Med (2010) 362: 1675-1685

Liver enzymes

-40

-30

-20

-10

0

Ch

an

ge

(U

/L)

0 24 48 72 96

Weeks

Placebo Vitamin E Pioglitazone

ALT

N Engl J Med (2010) 362: 1675-1685

Change in body weight

-2.5

02

.55

Ch

an

ge

(kg

)

0 24 48 72 96

Weeks


WEIGHT

N Engl J Med (2010) 362: 1675-1685

Who should we treat with vitamin E? Should we look for low vitamin E levels? Does reduction in the ALT mean the patient is

responding?

Who should we treat with vitamin E?

Loomba et al, AASLD 2010

Vit E treated

• Responders didn’t have low initial vitamin E levels

• The increase in vitamin E did not correlate with response

• Non-compliance did not explain non-response



Placebo

• Responders didn’t have low initial vitamin E levels

• The increase in vitamin E did not correlate with response

• Non-compliance did not explain non-response

Vit E treated



• ALT dropped a bit more in responders than placebo

• ALT dropped in both responders and non-responders

Responders

Non-responders

P = 0.005

PIVENS trial summary

Vitamin E helped in about half the patients Non-cirrhotic, non-diabetic Natural vitamin E, 800 IU/day We don’t know why it works We can’t predict who will respond or who is

responding Pioglitazone helped a bit less that half the

patients Non-cirrhotic, non-diabetic Weight gain is a problem Long-term safety is still an issue

NASH CRN TONIC trial

Treatment of NAFLD in Children = TONIC NASH Clinical Research Network study Hypothesis: metformin and vitamin E are

superior to placebo for the treatment of NAFLD

Lavine et al, JAMA (2011) 305: 1659-1668

TONIC trial Multicenter, double masked, double placebo,

randomized

Metformin 500 mg bid + vitamin E placebo

orVitamin E (natural form) 400 IU bid + metformin

placeboorBoth placebos bid

Treatment duration: 2 years A priori endpoint: change in ALT Secondary endpoint: histology

Lavine et al, JAMA (2011) 305: 1659-1668

TONIC: changes in primary endpoint (ALT)

Metformin

Placebo

Vitamin E

ALT

Lavine et al, JAMA (2011) 305: 1659-1668

TONIC: changes in primary endpoint (ALT)

Metformin

Placebo

Vitamin E

ALT

No significant differences

Lavine et al, JAMA (2011) 305: 1659-1668

Vitamin E increased resolution of NASH(from initial definite or borderline NASH)

TONIC results: Liver biopsy changes

Lavine et al, JAMA (2011) 305: 1659-1668

% with resolution of NASH

P = 0.006N.S.

TONIC trial summary Vitamin E helped about half the children

Primary endpoint of ALT change not met (placebo improved)

Biopsies did improve 800 IU of natural vitamin E daily

Metformin did not help

Lavine et al, JAMA (2011) 305: 1659-1668

Treatment of NASH 2011 Focus on preventing adipose IR and

associated systemic lipotoxicity Doing this treats NASH and comorbidities

Lifestyle modification Exercise: Goal of 30-45 minutes aerobic daily Weight loss

gradual and sustained bariatric surgery an option

Healthy eating portion control avoid sugar sweetened beverages no trans-fats

Treatment of NASH 2011 Drugs

Vitamin E? Thiazolidinediones? (pioglitazone, rosiglitazone) Statins? Metformin-no benefit of improving hepatic insulin

sensitivity Not effective: ursodiol, betaine

Benefit of controlling co-morbidities on NASH? Recognize and treat obstructive sleep apnea Treating hyperlipidemia, improving glycemic

control: no effect on liver

Future directions

Incretin mimetics? Naturally occurring: GIP, GLP-1

Made by enteroendocrine L-cells Responsible for 70% of post-prandial insulin secretion Delays gastric emptying, increases satiety Peripheral effects?

Analogue: exenetide Inhibit breakdown by inhibiting DPP-4: gliptins

(sitagliptin, saxagliptin) FXR ligands?

Farnesoid X receptor = nuclear receptor activated by bile acids

FXR agonist for NASH

FXR = “Farnesoid X receptor” = ligand activated nuclear receptor

Bile acids are the major natural ligands Increased bile acids decreased synthesis,

increased export


BA

Cholesterol

BA

Gut

BABA = Bile acids


BA

Cholesterol

BA

Gut

BA

FGF19 synthesis

by enterocytes

BA = Bile acids

FGF=Fibroblast growth factor

FXR = Farnesoid X receptor

FXR

BA + FXR

Exporters(MDRs, BSEP)

TGR5Bile acid receptor

Hepatic and peripheral effects

Regulation of gene expression by FXR

Neuschwander-Tetri, B. A. Curr Gastroenterol Rep (2012) 14: 55-62


High affinity FXR ligand

Research options at SLU NASH Clinical Research Network studies

NASH CRN treatment trials FLINT (FXR Ligand in the Treatment of NASH) Enrolling now!

“Database” observational study, seeking: Ideally patients suspected of having NAFLD but not

yet biopsied Can enroll with a biopsy < 3 months old Annual visits with free lab tests until 2014

[email protected]

Pathogenesis of NASH: A Two “Hit” Hypothesis

Festi, et al. Ob Rev. 2004; 5: 27- 42

2nd Hit

FFAsLipid PeroxidationROSScavengers

TNF ATPIKK NF-kEndotoxin IL-6

OBESITY DyslipidemiaType 2 Diabetes

FFAsHyperinsulinemiaInsulin sensitivityLeptin sensitivityAdiponectin effectFAT STORAGE 1st Hit

InflammationNecrosisApoptosis

LeptinLPO end productsTNF

HSCs activation

FIBROSIS

Day CP. Liver International 2006

Fibrosis &

cirrhosis

Steatosis

Steatohepatitis

Normal

Genes

Environment

Oxidative Stress,

cytokine, & endotoxin

related genes

Steatosis genes

Fibrosis genes

Environmental Factors Alcohol intake

Low is protective Dietary factors Low antioxidant

vitamins saturated fat

Obesity * Food intake Lack of exercise Type II DM* Small bowel

bacterial overgrowth Sleep apnea

syndrome

*Have a genetic component*Have a genetic component

Wilfred de Alwis, NM & CP Day Wilfred de Alwis, NM & CP Day Seminars Liv dsSeminars Liv ds. . 20072007

Hypothesis

Both pioglitazone and vitamin E are superior to placebo for the treatment of NASH.

NASH CRN

Specific Aim To perform a prospective multicenter,

double-masked, double-placebo, randomized clinical trial of pioglitazone (30 mg/day) or vitamin E (rrr α tocopherol 800 IU/day) versus placebo pioglitazone provided by Takeda

under a CRADA vitamin E provided by Pharmavite

under a clinical trials agreement

NASH CRN

Inclusion and exclusion criteria Inclusion criteria:

Alcohol consumption < 20 gm/day for women and 30 gm/day for men

Biopsy proven steatohepatitis within last 6 months

NAFLD activity score: ≥ 5 with definite or

probable steatohepatitis =4 + definite

steatohepatitis agreed by 2/3 pathologists

Exclusion criteria: Diabetes mellitus Cirrhosis Prior bariatric surgery Any drug therapy for

NASH between biopsy and randomization

Presence of other liver diseases

NASH CRN

Study Design

placebo

Pioglitazone (30 mg/day)

Vitamin E (rrr α-tocopherol) 800 IU/day

RandomizationEligibility assessed by local pathologist

(1:1:1)Wk 0

Month -6

End of treatmentLiver Biopsy

Wk 96

Week 120end of study

Liver biopsy

NASH CRN

Plan of Analysis(all histologic analyses on blinded central review of deeper cuts of baseline liver

biopsy & end of treatment biopsy) Primary endpoint:

Decrease in NAS by 2 or more points, with at least a 1 point drop in ballooning, and no worsening of fibrosis

2 Primary comparisons of proportion of subjects who met endpoint: Vitamin E vs placebo Pioglitazone vs placebo

Significance set at p< 0.025

Secondary endpoints: changes in individual histologic features resolution of steatohepatitis changes in anthropometrics, insulin resistance, quality of life adverse events

NASH CRN

Baseline Characteristics

Means or %s

Vitamin E

N= 83

Placebo

N= 84

Pioglitazone

N= 80

Age (yrs)

Female (%)

Caucasian (%)

BMI (Kg/m2)

Waist circumference (cm)

AST (IU/L)

ALT (IU/L)

AP (IU/L)

Bilirubin (mg/dl)

Triglycerides (mg/dl)

IR (HOMA-IR)

46.6

61

66

34

107

59

86

77

0.7

166

5.2

45.4

58

81

35

109

55

81

82

0.7

165

5.5

47

59

74

34

108

54

82

86

0.7

162

5.0

NASH CRN

Baseline histology

Vitamin E

Mean or %

Placebo

Mean or %

Pioglitazone

Mean or %

Steatosis grade

Inflammation grade

Ballooning grade

Fibrosis stage

NAFLD activity score (NAS)

1.9

1.8

1.3

1.5

5.1

1.9

1.6

1.3

1.6

4.8

2

1.8

1.1

1.4

5

% without ballooning on central review of deeper cuts of baseline biopsy

18 17 27

blinded central review ofdeeper cuts of baseline liver biopsy

NASH CRN

Primary Outcome –Vitamin E alone met the pre-specified primary endpoint

Vit E placebo Pio0

10

20

30

40

50

treatment groups

Pro

po

rtio

n o

f su

bje

cts

(%)

P< 0.001 P< 0.04

36/84NNT=4.4

26/80NNT= 6.6

16/83

NASH CRN

Both Vitamin E and Pioglitazone improve steatosis

-40

-20

0

20

40

60

80

pro

po

rtio

n o

f su

bje

cts

(%)

wo

rsen

ed

i

mp

rove

d P< 0.001 P<0.0001

Vit E placebopioglitazone

Δ grade0.1

Improvement in severity of steatosis gradeVit E vs placebo: p< 0.0001Pio vs placebo: p< 0.0001

Δ grade0.7

Δ grade0.8

NASH CRN

Both Vitamin E and Pioglitazone improve lobular inflammation

-60

-40

-20

0

20

40

60

80

pro

po

rtio

n o

f su

bje

cts

(%)

wo

rsen

ed

im

pro

ved p< 0.01 p< 0.001

Vit Eplacebo

pioglitazone

Improvement in severity of inflammation:Vitamin E vs placebo: p< 0.008Pioglitazone vs placebo: p< 0.0009

Δ grade0.6

Δ grade0.2

Δ grade0.7

NASH CRN

Both Vitamin E and Pioglitazone improve the severity of ballooning and

the proportion of subjects whose ballooning improves

-60

-40

-20

0

20

40

60

80

pro

po

rtio

n o

f su

bje

cts

(%)

wo

rsen

ed

im

pro

ved

P<0.02 P<0.02

Vit Eplacebo

pioglitazone

Δ grade0.5

Δ grade0.4

Δ grade0.2

Improvement in severity (grade) of ballooning:Vit E vs placebo: p< 0.01Pioglitazone vs placebo: 0.03

NASH CRN

Both vitamin E and pioglitazone increased the proportion of subjects with

resolution of NASH

Vitamin E placebo pioglitazone0

20

40

60

80

100

study groups

pro

po

rtio

n o

f su

bje

cts

(%)

P< 0.0008 P< 0.01

44/84

23/83

40/80

NASH CRN

Mutually exclusive categorization of reasons for not meeting primary outcome

Categories

Vit E

N=48/84

Placebo

N=67/83

Pio

N=53/80

No follow up biopsy

Worsening of fibrosis score

Failure to improve NAS ≥ 2

Failure to meet primary outcome due to ballooning score=0 at baseline

4

15

22

7

11

16

35

5

10

12

20

11

NASH CRN

Neither Vitamin E nor Pioglitazone improved fibrosis scores or proportion of subjects with

improved fibrosis

-60

-40

-20

0

20

40

60

pro

po

rtio

n o

f su

bje

cts

(%)

wo

rsen

ed

i

mp

rove

d

Vitamin E placebopioglitazone

n.s. n.s.

Δ grade0.3 Δ grade

0.1

Δ grade0.4

Improvement in severity of fibrosis scores:Vit E vs placebo: p= 0.19 (n.s.)Pioglitazone vs placebo: p=0.1 (n.s.)

NASH CRN

Liver enzymes-4

0-3

0-2

0-1

00

Ch

an

ge

(U

/L)

0 24 48 72 96

Weeks


ALT

NASH CRN

Insulin resistance-1

01

Ch

an

ge

([m

g/d

L x

µU

/mL

]/4

05

)

0 48 96

Weeks


HOMA-IR

NASH CRN

Change in body weight-2

.50

2.5

5

Ch

an

ge

(kg

)

0 24 48 72 96

Weeks


WEIGHT

NASH CRN

Adverse eventsAdverse event Vitamin E Placebo Pioglitazone

Total SAE

Drug-related SAE

Deaths

ALT > 500 IU/l

Bili > 3 mg/dl

CVD events

New onset T2DM

Bone fractures

Bone ΔT > -1

7

0

1

0

1

12

4

3

0

10

0

0

0

0

12

0

5

0

2

0

0

0

2

10

0

3

1

NASH CRN

Summary -1 Vitamin E (800 IU/day), but not pioglitazone

(30 mg/day), was superior to placebo for histological improvement as defined in the primary outcome measure

Both vitamin E and pioglitazone significantly improved: Steatohepatitis Steatosis grade Inflammation grade NAFLD activity score

Neither drug improved fibrosis scores significantly

NASH CRN

Summary -2

Pioglitazone improved insulin sensitivity, but was associated with weight gain

There were no study drug related SAEs

NASH CRN

Vitamin E is superior to placebo for the treatment of active NASH in nondiabetic adult patients.

Pioglitazone did not meet the primary outcome for histological improvement, but significantly improved other key histological features of NASH.

Neither drug improved fibrosis Both agents were relatively safe over the 96

week study, although pioglitazone was associated with weight gain

Conclusions

NASH CRN

Treatment Of Nonalcoholic steatohepatitis In Children

(TONIC)

The NIDDK Clinical Research Network

(NASH CRN)

Hypothesis

Both metformin and vitamin E are superior to placebo for the treatment of NAFLD

NASH CRN

Specific Aim

To perform a multicenter, double-masked, double-placebo, randomized clinical trial of metformin (500mg BID) or vitamin E (RRR-a-tocopherol 400 IU BID) versus placebo for the treatment of NAFLD Over-encapsulated generic metformin/placebo Vitamin E/placebo provided by Pharmavite under

a Clinical Trials Agreement (CRADA)

NASH CRN

Inclusion and exclusion criteria

Inclusion criteria: Boys & girls 8-17yo Biopsy proven NAFLD

within 6 mos ALT>60 U/L at

randomization and 1-12mos prior

Able to swallow pills Informed consent/assent Complete screening in

112 days

Exclusion criteria: Diabetes mellitus Cirrhosis Prior bariatric surgery Significant alcohol ALT>400 Presence of other liver

diseases Pregnancy/nursing Any drug tx for NASH in

the 3mos prior to randomization

NASH CRN

Hypothesis

Both metformin and vitamin E are superior to placebo for the treatment of NAFLD

NASH CRN

NASH CRN

Specific Aim



NASH CRN

Primary Outcome-neither treatment met criterion for sustained ALT reduction

NASH CRN

Specific Aim



NASH CRN

Vitamin E increased resolution of NASH

(from initial definite or borderline NASH)

NASH CRN



NASH CRN

Neither Vitamin E nor Metformin Improved Fibrosis Score

Specific Aim



NASH CRN

Final Conclusions NAFLD is the most common chronic liver

disease in the world & threatens our organ allocation system

Vitamin E, Pioglitazone, & Metformin do not improve fibrosis in NAFLD

Vitamin E improves ballooning and NAS scores in adults & children

Behavior modification & treatment of underlying obesity is imperative

www.kampkaana.org

Demographics & physical characteristics (n=39)Parameters Mean

Gender 25 females14 males

Ethnicity 15 Whites12 Hispanics

11 Blacks1 Asian

Age (y) 11.9 ± 1.39*

Weight (kg) 88.8 ± 18.6

Height (cm) 159.8 ± 7.3

BMI (kg/m2) 34.6 ± 6.1

FFM (kg) 49.8 ± 9.3

FM (kg) 39.1 ± 13.0

FM (%) 43.2 ± 7.4

Wt z-score 2.65 ± 0.60

BMI z-score 2.38 ± 0.31

Wt percentile 98.8 ± 1.9

BMI percentile 98.9 ± 0.9

Changes in anthropometric & body composition post camp

-6

-5

-4

-3

-2

-1

0

1

2

3

P<0.01

P<0.01

P<0.01P<0.01

P<0.01

P<0.01

Fat(%)

Fat(kg)

FFM(kg)

BMIz-score

BMI

(kg/m2)Wt (kg)

Po

st C

am

p -

Pre

Ca

mp

Changes in IWQOL scores post camp

-5

0

5

10

15

20

P<0.01

P=0.60

P<0.03

P<0.01

P<0.02

TotalScore

FamilyRelations

SocialLife

BodyEsteem

PhysicalComfort

Po

st C

am

p -

Pre

Ca

mp

Changes in CDI scores post camp

-3.0

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

1.0

P=0.94

Inte

rper

sona

l

Proble

ms

P<0.05

P=0.10

P=0.07

P=0.77P=0.51

Total

Score

Negat

ive

Self E

steem

Anhed

onia

Inef

fecti

vene

ss

Negat

ive

Moo

dP

ost

Ca

mp

- P

re C

am

p

www.kampkaana.org

nonalcoholic fatty liver disease

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